Removing the Target Functional Group

There have been some successes in modifying existing aminoglycoside antibiotics to generate new compounds that bind, but are not inactivated

Tobramycin (3'-deoxykanamycin B)

dibekacin (3',4'-dideoxykanamycin B)

Fig. 5 Structures of the aminoglycosides tobramycin (top) and dibekacin (bottom). Both molecules lack a 30-hydroxyl group, making them resistant to modification by APH(30)-IIIa by, resistance enzymes. For example, tobramycin (3'-deoxykanamycin B) (Umezawa et al. 1971b) and dibekacin (3',4'-dideoxykanamycin B) (Umeza-wa et al. 1971a), both lacking the 3'-hydroxyl, are competitive inhibitors for APH(3')s (McKay and Wright 1995) (Fig. 5). Both molecules evade modification by the APH(3') enzymes. However, they can be deactivated by other classes of aminoglycoside-modifying enzymes.

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